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Article Dans Une Revue Comparative Biochemistry and Physiology - Part D: Genomics and Proteomics Année : 2023

Peptidomic analysis of the host-defense peptides in skin secretions of the Amazon river frog Lithobates palmipes (Ranidae)

Milena Mechkarska
Gervonne Barran
  • Fonction : Auteur
Jolanta Kolodziejek
  • Fonction : Auteur
Laurent Coquet
Thierry Jouenne
Norbert Nowotny
  • Fonction : Auteur
J. Michael Conlon
  • Fonction : Auteur
  • PersonId : 1043956

Résumé

Envenomation by the Trinidad thick-tailed scorpion Tityus trinitatis may result in fatal myocarditis and there is a high incidence of acute pancreatitis among survivors. Peptidomic analysis (reversed-phase HPLC followed by MALDI-TOF mass spectrometry and automated Edman degradation) of T. trinitatis venom led to the isolation and characterization of three peptides with antimicrobial activity. Their primary structures were established asTtAP-1 (FLGSLFSIGSKLLPGVFKLF-SRKKQ.NH2), TtAP-2 (IFGMIPGLIGGLISAFK.NH2) and TtAP-3 (FFSLIPSLIGGLVSAIK.NH2). In addition, potassium channel and sodium channel toxins, present in the venom in high abundance, were identified by CID-MS/MS sequence analysis. TtAP-1 was the most potent against a range of clinically relevant Gram-positive and Gram-negative aerobes and against the anaerobe Clostridioides difficile (MIC = 3.1-12.5 µg/mL). At a concentration of 1× MIC, TtAP-1 produced rapid cell death (<15 min against Acinetobacter baumannii and Staphylococcus aureus). The therapeutic potential of TtAP-1 as an anti-infective agent is limited by its high hemolytic activity (LC 50 = 18 µg/mL against mouse erythrocytes) but the peptide constitutes a template for the design of analogs that maintain the high bactericidal activity against ESKAPE pathogens but are less toxic to human cells. It is suggested that the antimicrobial peptides in the scorpion venom facilitate the action of the neurotoxins by increasing the membrane permeability of cells from either prey or predator.
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Dates et versions

hal-04294874 , version 1 (27-11-2023)

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Milena Mechkarska, Gervonne Barran, Jolanta Kolodziejek, Laurent Coquet, Jérôme Leprince, et al.. Peptidomic analysis of the host-defense peptides in skin secretions of the Amazon river frog Lithobates palmipes (Ranidae). Comparative Biochemistry and Physiology - Part D: Genomics and Proteomics, 2023, 46, pp.101069. ⟨10.1016/j.cbd.2023.101069⟩. ⟨hal-04294874⟩
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